Deconstructing spinal cord injury to understand potential cures

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When asked which function they would like to regain, many individuals with spinal cord injuries say that they would like to regain the ability to have sex, with their desire to restore bladder function coming in as a close second.

“That’s something I guess I wouldn’t understand as someone who can walk, but I guess you lose a part of yourself and you’re so dependent on other people that your first instinct isn’t ‘I want to walk again,’ it’s ‘I want to be my own person again,’” said fourth-year student Tara Phuongnhi Tran.

Tran, who works in Case Western Reserve University School of Medicine Professor of Neuroscience Jerry Silver’s research laboratory, is currently working on a study using animal models to better understand spinal cord injury and proposed therapeutic treatments.

The team of researchers, led by Silver, is in the process of conducting a pre-clinical trial to assess the effectiveness of intracellular sigma peptide (ISP), a protein that has demonstrated a promising ability to restore function in cases of spinal cord injury in rats, some of which regained the ability to urinate, move, or both in a previous trial.

There are no modern, effective drug therapies that facilitate natural recovery from spinal cord injuries, but ISP has proven to have profound implications for this type of recovery and rehabilitation.

In the study, researchers are working to use ISP in combination with bone marrow-derived multipotent adult progenitor cells (MAPC) to enhance recovery in rodents that have spinal cord injuries.

Tran is actively involved in two central aspects of the study; the first is related to assessing bladder and motor function in the animal models, and the second is related to understanding the sub-cellular processes involved with spinal cord injury treatment and regeneration.

The blind study currently uses 56 rats. The animals undergo surgical operations to debilitate their spinal cord function, which serves as a replication of what occurs in humans who suffer from spinal cord injuries. The animals are injected regularly with ISP, MAPC or both, and their recovery is charted and analyzed in regard to their recovery of bladder function, motor function, both or neither.

“We use something called metabolic cages, where we put [the rats] in this cage and it measures how often and how much they [expel waste],” said Tran. “We score them objectively on how well they can walk, how they’ve regained function, and then we also do grid walk, where we put them literally on this grid and we see how many times their feet fall within this grid [to] measure coordination.”

According to Tran, MAPC tends to work best in the short-term while ISP works better for long-term injuries. One of the key issues at hand is to ascertain whether or not these drug therapies will work for individuals who have sustained recent spinal cord injuries or those who have had them for a longer period of time.

At the sub-cellular level, Tran is working to understand how individual cells are affected by the drug therapies.

“I personally don’t like the sub-cellular level because with [animal models], you can see them get better, you can see them regain function and it’s exciting,” said Tran. “With the cells, you don’t really see improvement.”

Tran also expressed how spinal cord injury is under-studied and underfunded, especially since there are no specific cures.

“If I cracked a nail or if I sprained an ankle … the human body is amazing because it regenerates,” said Tran. “But for some reason, there’s something about the spinal cord that doesn’t, which is why it’s an issue. This research is amazing because right now, there’s really no cure to spinal cord injury.”

Tran added that while there are symptomatic controls and treatments like wheelchair usage and targeted surgeries, the Silver Lab’s potential discovery of a specific cure to spinal cord injury in the form of an injection would have the potential to alter many lives.

“Spinal cord injury, while it doesn’t affect as many people, it completely alters their standard of living and changes how they live,” said Tran. “This is something I wish we had more awareness about … [people with spinal cord injuries] can’t be advocates for themselves, which is why we try to advocate for them.”

Tran, who is pursuing undergraduate degrees in chemistry and medical anthropology and a master’s degree in bioethics through the Integrated Graduate Studies program, hopes to attend law school in the future. She would like to study intellectual property law, which she feels will provide her a way to incorporate her multifaceted undergraduate academic experience.

For now, Tran would like to continue to contribute time to the spinal cord injury research conducted in the Silver Lab and assist the research team in their efforts to assess their novel therapeutic drug treatment.

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